The Scripps Research Institute

University of Florida Research Foundation Inc

Derek R Duckett

William R Roush

Theodore M Kamenecka

Rong Jiang

Xinyi Song

Philip LoGrasso

Michael Darin Cameron

John L Cleveland

Laura H Rosenberg

Andrii Monastyrskyi

The invention provides compounds and methods of inhibiting a cyclin-dependent kinase, comprising contacting the cyclin-dependent kinase and an effective amount or concentration of a compound of formula (I) wherein variables are as defined herein. Compounds of formula (I) can be highly selective inhibitors of cyclin-dependent kinases such as CDK12/13, relative to other kinases such as casein kinases, such as CK1&#x3b4;/&#x3b5;. Compounds can be used in treatment of cancers, such as breast cancer, brain cancer and ovarian cancer. 

Small molecule inhibitors of CDK12/CDK13

The invention provides a method of inhibiting casein kinase 1&#x3b4; (CK1&#x3b4;), comprising contacting the CK1&#x3b4; with a compound of formula (I), as defined herein; such as compound SR-3029. We demonstrate that CSNK1D is amplified and/or overexpressed in human breast tumors and that CK1&#x3b4; can be medically targeted in human breast cancer subtypes overexpressing this kinase. The invention further provides a method of treating cancer, such as a breast cancer, melanoma, glioblastoma, medulloblastoma, renal, bladder or colon cancer, or a cancer that metastasizes to the brain, lung, or bone provided that both elevated CK1&#x3b4; and &#x3b2;-catenin dependence are involved in those metastatic diseases. The cancer can be a breast cancer of the triple negative subclass of breast cancers (TNBC), or can be an HER+ breast cancer.

Therapeutic targeting of casein kinase 1&#x3b4; in breast cancer

The present invention provides novel substituted pyrimidinyl-amines that are useful as inhibitors of protein kinases, especially c-Jun N-terminal kinases (JNK) and pharmaceutical compositions thereof and methods of using the same for treating conditions responsive to the inhibition of the JNK pathway.

Substituted pyrimidinyl-amines as protein kinase inhibitors

Growing community of inventors

Jupiter, FL, United States of America

Derek R Duckett